Intestinal inflammatory diseases (IID) are a family of chronic, idiopathic, recurrent and tissue-destructive diseases, characterized by the dysfunction of mucous cells T CD4+ and CD8+, altered production of cytokines and cellular inflammation, leading to prolonged and sometimes irreversible damage of the gastrointestinal function and structure, more precisely, in the distal portion of the large intestine and colonic mucosa. The main IID that occurs in humans are subdivided into two phenotypes: Crohn's disease and ulcerative colitis.
Crohn's disease is a chronic disease characterized by transmural and granulomatous inflammation, which can cause inflammation in any segment of the digestive tract, as a result of disorderly immune responses against intraluminal antigens derivatives of the commensal bacterial flora in genetically susceptible individuals.
Ulcerative colitis occurs as a consequence of a recurrent acute or chronic intestinal inflammatory disease and is confined to the entire intestine, starting in the rectum and progressing, apparently, continuously affecting other intestinal portions.
Both Crohn's disease and ulcerative colitis are accompanied by clinical symptoms such as diarrhea, rectal prolapse, weight loss and abdominal pains, and are histologically characterized by inflammation and ulceration of the colonic mucosa.
Studies on the pathogenesis of IID and the potential therapeutic agents for treating these diseases has been of major importance over recent decades. It is known that the severity of the intestinal inflammatory process may be a consequence of the decrease of the regulation mechanisms involved in the homeostasis of the intestinal mucosa, and many of these processes have been attributed to the deficiency of the production of one of the main cytokines involved in regulating inflammatory responses of the organism, IL-10. The importance of this cytokine in regulating the immunity of the intestinal mucosa has been demonstrated by the development of IID in mice with a deficiency of IL-10 (FIOCCHI C. Inflammatory bowel disease: etiology and pathogenesis. Gastroenterology, 115: 182-205, 1998).
The clinical importance of the expression of IL-10 is supported by studies that show that the immunological increase of this cytokine prevents inflammation and damage to the mucosa, in colitis animal models and in humans. This meant that the cytokine system became an object of interest that was promising for the development of clinically relevant anti-inflammatory drugs.
It is further known that in IID and acute and chronic inflammations such as rheumatoid arthritis, SIRS and psoriasis, an imbalance occurs between pro-inflammatory and anti-inflammatory cytokines, in particular, increased levels of pro-inflammatory cytokines are detected, such as IL-1, IL-6, IL-8, IL-12, TNF-α and IFN-β, which are secreted by macrophages, lymphocytes, and polymorphonuclear neutrophils. This activity leads to an amplification of the inflammatory cascade and to the secretion of more inflammatory mediators, enzymes and free radicals that cause tissue injury and are implied in the pathogenesis of IDD alterations, such as diarrhea, mucosal permeability and fibrosis, and also in the pathogenesis of acute and chronic inflammations such as in rheumatoid arthritis.
Given the potent immunosuppressive effects of the cytokine IL-10, it began to be examined as a potentially therapeutic agent for the IID and other acute or chronic inflammatory diseases, in humans. In this context, it has been widely demonstrated that many compound derivatives of plants present significant anti-inflammatory effects. This is why they represent potential agents for the development of new drugs, especially intended for the treatment of control of chronic inflammatory states.
Matrine, for example, is an alkaloid found in plants of the Sophora genus, and proved to have anti-inflammatory effects in colitis-induced mice by trinitrobenzene sulfonic acid (TNBS), probably by regulating the production of colonic TNF-α(CHENG, H.; XIA, B.; ZHANG, L.; ZHOU, F.; ZHANG, Y. X.; YE, M.; HU, Z. G.; LI, J.; WANG, Z. L.; LI, C.; GUO, Q. S. Matrine improves 2,4,6 trinitrobenzene sulfonic acid-induced colitis in mice. Pharm. Res., 53(3): 202-208, 2005). Another example is the root extract of plants of the Poligalae (Polygala tenuifolia) genus, which is a medicinal plant that proved to have a preventive action on TNBS-induced colitis probably by regulating the production of IFN-γ and IL-4.
Moreover, the natural latex of the rubber tree Hevea brasiliensis has been studied for a long time, chiefly due to its angiogenic and healing properties. This material showed that it produced increased vascularization, epithelization, accelerating the process of granulation of chronic wounds of various etiologies and complete healing in a shorter time and at a lower cost, when compared to those available on the market.
Hence, by developing a protein preparation derivative of the latex of Hevea brasiliensis, and a composition containing it, the present invention provides desirable results in the combat and prevention of acute or chronic inflammatory diseases.